Use of CT simulation and 3-D radiation therapy treatment planning system to develop and validate a total-body irradiation technique for the New Zealand White rabbit

Abstract

Purpose

Well-controlled ionizing radiation injury animal models for testing medical countermeasure efficacy require robust radiation physics and dosimetry to ensure accuracy of dose-delivery and reproducibility of the radiation dose-response relationship. The objective of this study was to establish a simple, convenient, robust and accurate technique for validating total body irradiation (TBI) exposure of the New Zealand White rabbit.

Methods

We use radiotherapy techniques such as computed tomography simulation and a 3 D-conformal radiation therapy treatment planning system (TPS) on three animals to comprehensively design and preplan a TBI technique for rabbits. We evaluate the requirement for bolus, treatment geometry, bilateral vs anterior-posterior treatment delivery, the agreement between monitor units calculated using the TPS vs a traditional hand calculation to the mid-plane, and resulting individual organ doses.

Results

The optimal technique irradiates animals on the left-decubitus position using two isocentric bilateral parallel-opposed 6 MV x-ray beams. Placement of a 5 mm bolus and 8.5 mm beam spoiler was shown to increase the dose to within ≤5 mm of the surface, improving dose homogeneity throughout the body of the rabbit. A simple hand calculation formalism, dependent only on mid-abdominal separation, could be used to calculate the number of monitor units (MUs) required to accurately deliver the prescribed dose to the animal. For the representative animal, the total body volume receiving > 95% of the dose, V_95% > 99%, V_100% > 95%, and V_107% < 20%. The area of the body receiving >107% of the prescribed dose was mainly within the limbs, head, and around the lungs of the animal, where the smaller animal width reduces the x-ray attenuation. Individual organs were contoured by an experienced dosimetrist, and each received doses within 95–107% of the intended dose, with mean values ∼104%. Only the bronchus showed a maximal dose >107% (113%) due to the decreased attenuation of the lungs. To validate the technique, twenty animals were irradiated with four optically-stimulated luminescence dosimeters (OSLDs) placed on the surface of each animal (two on each side in the center of the radiation beam). The average dose over all animals was within <0.1% from intended values, with no animal receiving an average dose more than ±3.1% from prescription.

Conclusion

The TBI technique developed in this pilot study was successfully used to establish the dose-response relationship for 45-day lethality across the dose-range to induce the hematopoietic-subsyndrome of the acute radiation syndrome (ARS).

Keywords:

• Acute radiation syndrome (ARS)
• radiation physics
• total body irradiation (TBI)
• animal model organisms
• models of radiation responses
• rabbits

Acknowledgements

The authors dedicate this article to the memory of Dr Karl Prado, who developed the preclinical physics and dosimetry program in radiobiology at the University of Maryland.

Disclosure statement

The authors declare no conflicts of interest related to the data generated within this study. Drs. Isabel L. Jackson and Zeljko Vujaskovic are scientific advisors to Humanetics Corporation.

Data availability

Raw data were generated at the University of Maryland School of Medicine. The authors confirm that all data supporting the findings of this study will be archived at the UMSOM for up to 5-years post-publication, and are available from the corresponding author (Yannick Poirier), upon reasonable request, and with approval by the Biomedical Advanced Research and Development Authority, Office of the Assistant Secretary for Preparedness and Response, Department of Health and Human Services. While the Biomedical Advanced Research and Development Authority funded the study, the study’s conclusions are those of its authors alone.

Additional information

Funding

This project has been funded in whole with federal funds from the Biomedical Advanced Research and Development Authority, Office of the Assistant Secretary for Preparedness and Response, Department of Health and Human Services under Contract #HHSO100201500009I, Task Order Number HHSO10033001T, entitled ‘Establishment of a rabbit model of ionizing radiation-induced thrombocytopenia, coagulopathies, and measures of associated vascular and organ injury’.

Notes on contributors

Yannick Poirier

Yannick Poirier is an Assistant Professor and Board-certified Clinical Medical Physicist in the Department of Radiation Oncology, Division of Medical Physics and Division of Translational Radiation Sciences at the University of Maryland School of Medicine. He oversees the dosimetry and physics of all radiation biological studies of the Division of Translational Radiation Sciences.

Charlotte Prado

Charlotte Prado was a Board-certified Medical Dosimetrist at the Division of Translational Radiation Sciences at the University of Maryland School of Medicine. She has participated in a large number of rabbit and non-human primate studies over the years, contouring organs, performing treatment planning system dose calculations in whole body or whole thorax lung irradiations

Karl Prado

Karl Prado was a Full Professor and a Board-certified Clinical Medical Physicist in the Department of Radiation Oncology, Division of Medical Physics, University of Maryland School of Medicine. He was Associate Director of the Division of Medical Physics and developed the dosimetry of irradiation protocols in non-human primates and murine biological studies of the Division of Translational Radiation Sciences.

Emily Draeger

Emily Draeger was a Research Medical Physicist in the Division of Translational Radiation Sciences at the University of Maryland School of Medicine during the course of the study. She is currently an Assistant Professor at the Department of Therapeutic Radiology at Yale University School of Medicine.

Isabel L Jackson

Isabel Lauren Jackson is an Associate Professor, Radiation Biologist, and Deputy Director of the Division of Translational Radiation Sciences, Department of Radiation Oncology, at the University of Maryland School of Medicine. She is the Director of the division's Medical Counter Measures program.

Zeljko Vujaskovic

Zeljko Vujaskovic is a Full Professor in the Clinical Division and Director of the Division of Translational Radiation Sciences, Department of Radiation Oncology, University of Medicine School of Medicine.